Cancer Management and Research (Jan 2022)
Hypoxic Breast Cancer Cell-Derived Exosomal SNHG1 Promotes Breast Cancer Growth and Angiogenesis via Regulating miR-216b-5p/JAK2 Axis
Abstract
Gaosai Dai,1 Yupeng Yang,2 Shuhao Liu,3 Huantao Liu1 1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong, 250200, People’s Republic of China; 3Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Huantao LiuDepartment of Breast Surgery, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People’s Republic of ChinaEmail [email protected]: Hypoxia is an important process that involved in the tumor microenvironment. In addition, hypoxic tumor cell-derived exosomes could promote tumor growth and angiogenesis. Thus, we aimed to investigate whether exosomes could regulate tumor development and progression under hypoxia in breast cancer.Methods: The level of SNHG1 in hypoxic breast cancer cells and exosomes derived from hypoxic breast cancer cells was determined by real-time qPCR assay. Bioinformatics prediction and dual-luciferase reporter assays were used to determine the interaction between SNHG1, miR-216b-5p and JAK2.Results: We found that comparing with exosomes derived from normoxia breast cancer cells, exosomes derived from hypoxic breast cancer cells could promote the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). In addition, SNHG1 level was significantly upregulated in exosomes derived from hypoxic breast cancer cells. Moreover, exosome-mediated delivery of SNHG1 siRNA3 markedly reversed the effects of exosome-mediated delivery of SNHG1 on HUVECs. Mechanically, SNHG1 could increase the level of JAK2 by competitively binding to miR-216b-5p. Additionally, exosome-mediated delivery of SNHG1 was found to promote breast cancer growth in vivo.Conclusion: Collectively, our study revealed that exosomal SNHG1 from hypoxic breast cancer cells could promote tumor angiogenesis and growth via regulating miR-216b-5p/JAK2 axis, suggesting that SNHG1 may serve as a potential therapeutic target for breast cancer.Keywords: breast cancer, exosomes, tumor microenvironment, hypoxia, long noncoding RNAs
